Immunodeficient mice refer to the mice with defects in one or more immune components (such as T, B, NK cells) in the immune system. This type of mouse is widely used in the research of oncology (tumor growth, metastasis, anti-tumor drug screening), immunology (mechanisms of immune cell development and proliferation, pathology of immune diseases), infectious diseases (pathogenic mechanisms of viral/bacterial infectious diseases), and stem cell biology (human stem cell transplantation), and more.
In 1962, the first mouse with immune dysfunction was found at Ruchill Hospital in Glasgow. They are called nude mice because they are hairless.
The FOXN1 gene is absent in nude mice. Lack of a functional thymus and T lymphocytes results in their adaptive immune response defected (including T cell-mediated immune response and helper T cell-mediated antibody formation). This means that they usually do not reject homologous transplants or xenografts, so nude mice are commonly used as recipients of human tumor xenografts.
However, nude mice still have B cells and NK cells (their NK cells are more active than wild-type mice), and the complete innate immunity to some extent limits the human cancer transplantation in nude mice. In addition, T cell leakage appears alongside aging of nude mice.
In 1980, Makino (Japan) found that non obese diabetic (NOD) mice suffered from T lymphocyte infiltration and islets β cell mass reduction, a hallmark of Type 2 Diabetes, which was accompanied with a variety of immune abnormalities, including complement deficiency and dysfunction of NK cells, macrophages, and dendritic cells.
In 1995, Shultz established non-obese diabetic (NOD)-severe combined immunodeficiency (SCID) mice by hybridizing NOD and SCID mice. NOD-SCID mice do not develop diabetes, lack T cells and B cells, and have inherent immune deficiency, so they become an ideal transplant recipients of human hematopoietic stem cells and human solid tumors.
In addition, Shultz et al. found that the immune leakage of SCID mice was as high as 90%, while that of NOD-SCID mice was less than 10%. As such, NOD-SCID mice have quickly become an indispensable transplantation model in hematopoietic cell research.
C-NKG mouse is a severely immune deficient strain independently developed with CRISPR/Cas9 to achieve IL2RG gene knockout on NOD/Shi-Scid mice.
C-NKG mice facilitate highly efficient human tumor cell line xenotransplantation (CDX) and human tumor tissue xenotransplantation (PDX). A variety of tissues can be efficiently transplanted into these mice, including human blood stem cells (HSC), peripheral blood mononuclear cells (PBMC), and more.
At present, the C-NKG model is recognized for a high degree of immunodeficiency for modeling tumors, immunity, autoimmune diseases, immunotherapy vaccine, GVHD / transplantation, safety evaluations and other research.
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